A gold nanostar-based SERS platform for point-of-care diagnostics of carbapenemase-producing enterobacteriacae

SPIE Proceedings Paper, April 29, 2017

Wei Cherng Malvin Kang; Yen Lynn Wong; Marek Piotrowski; Woon Pei Jeanette Teo; Shuai He; James Chen-Yong Kah

The ever-increasing spread and emergence of antibiotic resistance poses a serious threat to global public health. With the existence of Carbapenem-resistant Enterobacteriaceae (CRE) produced by the Klebsiella Pneumoniae bacteria, it renders the use of carbapenems, the last-resort class of β-lactam antibiotics, useless against combating against bacterial infections. Such infections reduce the ability to treat complex infections due to the lack of antibiotic options for treatment, leading to CRE-associated mortalities. Current methods of detection, like CarbaNP test and Modified Hodge’s Test, have significant limitations in that the time taken for detection of carbapenemase activity ranges between hours to days, and are non-specific in detecting the specific phenotype, making it challenging to isolate patients rapidly and to devise appropriate treatment for infected patients. We propose a methodology by utilising Surface Enhanced Raman Spectroscopy (SERS) to study bacterial β-lactamase activity. This is done via the use of gold nanostars (AuNS), which have reported excellent SERS properties, conjugated with a β-lactam antibiotic ceftriaxole, as a proof-of-concept study to analyse the changes in the SERS spectra associated with cleavage of the β-lactam ring upon interaction with the New Delhi Metalloproteinase (NDM)- producing Escherichia coli (Class B β-lactamase). We are able to obtain detection of carbapenemase activity within 25 minutes, with the associated changes in SERS spectra being diminishing of SERS peaks at 1358cm^-1 and 1495cm^-1. This project can be further extended to study the activity of other classes of β-lactamases and other β-lactam antibiotics to improve this state of technology for potential adoption by healthcare institutions.